Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
Org Lett. 2015 Feb 6;17(3):744-7. doi: 10.1021/acs.orglett.5b00038. Epub 2015 Jan 28.
The more cytotoxic, thermodynamically less stable (+)-attenol B was isolated as a minor isomer of the spiroketal attenol A and synthesized previously as a minor product. Herein, we report a new strategy that for the first time led to asymmetric synthesis of (+)-attenol B as an exclusive product, featuring sequential Achmatowicz rearrangement/bicycloketalization to efficiently construct the 6,8-dioxabicyclo[3.2.1]octane core. In addition, (-)-attenol A was obtained with 91% yield by isomerization of (+)-attenol B in CDCl3.
作为螺旋缩酮阿替洛尔 A 的次要异构体，毒性更大、热力学上更不稳定的 (+)-阿替洛尔 B 被分离出来，并以前作为次要产物被合成。在此，我们报告了一种新策略，该策略首次导致 (+)-阿替洛尔 B 作为唯一产物的不对称合成，其特征在于顺序 Achmatowicz 重排/双环缩酮化，以有效地构建 6,8-二氧杂双环[3.2.1]辛烷核心。此外，通过 (+)-阿替洛尔 B 在 CDCl3 中的异构化，(-)-阿替洛尔 A 以 91%的产率得到。
